In aquaculture, piscicides are used as fishing gear to combat parasitic, invasive fish species and eliminate dominant fish species in a water body. Therefore, assessment of piscicide activity is important. Hence, in this study, we have aimed to assess the piscicidal potential of Carica papaya leaves, seeds, and peel powder on juveniles of Clarias gariepinus using behavioural responses and mortality rate as the toxicity endpoints. Four hundred and fifty (450) juveniles of Clarias gariepinus were used for the 96-hour static bioassay. Five (5) different concentrations of 0 mgL-1, 25 mgL-1, 50 mgL-1, 75 mgL-1, and 100 mgL-1 containing ten (10) fish samples in triplicates were used. The physicochemical parameters of the test concentrations monitored during the exposure include Temperature, pH, Electrical Conductivity, Dissolved Oxygen, and Total Dissolved Solids. The results of the physicochemical parameters did not vary significantly compared with the control. The results of the behavioural responses showed a range of reactions, such as erratic swimming, gulping of air, loss of reflex, vertical orientation, loss of buoyancy, jumping, and discolouration. The fish mortality rate was used to determine the median lethal concentrations (LC50) of the leaves, seeds, and peel powder using the Probit method. The LC50 values estimated from Probit analysis were 147.17 mgL-1, 262.376 mgL-1, and 697.180 mgL-1, respectively. The results implied that of the three plant parts used, the leaves powder of Carica papaya showed the most promising piscicidal potential. Hence, this underscores screening whole plant parts to ascertain the most suitable for such desired activity. The substitutes of plant substances, which can act as ecologically friendly piscicides, can be encouraged against commonly used synthetic chemicals which can be detrimental to aquatic ecosystems.